Zhu Zilong, Chu Zhuze, Fei Fei, Wu Chenxi, Fei Zhengyue, Sun Yuxia, Chen Yun, Lu Peihua
The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi 214023, China.
Vaccines (Basel). 2025 Jan 13;13(1):64. doi: 10.3390/vaccines13010064.
In the past decade, immunotherapy has become a major choice for the treatment of lung cancer, yet its therapeutic efficacy is still relatively limited due to the various immune escape mechanisms of tumors. Based on this, we introduce Neo-BCV, a novel bacterial composite vaccine designed to enhance immune responses against lung cancer.
We investigated the immune enhancing effect of Neo-BCV through in vivo and in vitro experiments, including flow cytometry, RNA-seq, and Western blot.
We have demonstrated that Neo-BCV can promote Dendritic cells (DCs) maturation and induce DCs differentiation into pro-inflammatory subgroups, significantly enhancing cytotoxic T lymphocyte (CTL)-mediated anti-tumor responses. Transcriptome sequencing revealed that Neo-BCV exerts its effects by specifically inhibiting the JAK2-STAT3 signaling pathway, a crucial regulator of cancer progression, metabolism, and inflammation. Moreover, Neo-BCV significantly improved the immune microenvironment in both tumor and spleen tissues without inducing notable toxic effects in major organs.
These findings highlight Neo-BCV's potential as a safe and effective therapeutic strategy, offering a novel avenue for clinical translation in lung cancer immunotherapy.
在过去十年中，免疫疗法已成为肺癌治疗的主要选择，但由于肿瘤的各种免疫逃逸机制，其治疗效果仍然相对有限。基于此，我们引入了新型细菌复合疫苗Neo-BCV，旨在增强针对肺癌的免疫反应。
我们通过体内和体外实验，包括流式细胞术、RNA测序和蛋白质免疫印迹，研究了Neo-BCV的免疫增强作用。
我们已经证明，Neo-BCV可以促进树突状细胞（DC）成熟，并诱导DC分化为促炎亚群，显著增强细胞毒性T淋巴细胞（CTL）介导的抗肿瘤反应。转录组测序显示，Neo-BCV通过特异性抑制JAK2-STAT3信号通路发挥作用，该信号通路是癌症进展、代谢和炎症的关键调节因子。此外，Neo-BCV显著改善了肿瘤和脾脏组织中的免疫微环境，且未在主要器官中诱导明显的毒性作用。
这些发现突出了Neo-BCV作为一种安全有效的治疗策略的潜力，为肺癌免疫治疗的临床转化提供了一条新途径。
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